generics may involve different levels of change that people may be more, or
less, happy with. There is no implication that people who need the branded
drugs for medical reasons will have to take generics.
is that the appearance of your drugs may change. This, which may sound trivial,
may be the thing that matters most to some people.
Kamerow, associate editor of the British Medical Journal, commented in an
article last year: “Confusion may arise in patients when they find that their
dependably round yellow pill is now a green oblong. Patients, especially
elderly patients, use colour to identify their pills, and report great concern
when the appearance, packaging and labelling change. This…may lead to a
decrease in adherence.”5
one pill once a day may become two or more, either because the new suppliers,
as with nevirapine, do not make the higher-dose version, or because a
combination pill is split into its components. (Or two could become one:
generic companies already make combinations for the low-income countries that
you won’t find in the UK, and there’s no reason a company couldn’t make, say,
an efavirenz/lamivudine pill for the UK market from 2014.)
often concerned that splitting combination pills into their components will
result in lower adherence. While combination pills are undoubtedly popular
amongst both physicians and patients, especially in situations where patients
pay and a combination pill counts as a single medicine, there’s little evidence
that there’s any difference in outcome or adherence.
One study presented at the
Glasgow HIV drug therapy conference two years ago (funded by Atripla manufacturers Gilead) found that
people who took one pill a day were 60% more likely to miss fewer than one in
20 doses than those taking three or more pills a day.6 But that
study purely compared numbers of pills. People on one pill a day could only
have been on Atripla, but those on
three or more could have been on all sorts of combinations and would include a
much higher proportion of people who were treatment-experienced and had
recent study presented at the International AIDS Conference in July7
found no difference in adherence between people using single-tablet regimens
and multiple-tablet ones, as long as the regimen was a once-a-day one. Even
this, however, did not directly compare a fixed-dose pill with its component
last month8 found that patients prescribed single-pill regimens were
no more likely to take them than multi-pill ones. Eight per cent of patients
prescribed single pills failed to even fill their prescriptions compared with
10 to 12% taking other regimens (not a significant difference). This was,
however, in the USA,
where patients are more likely to be non-adherent for financial reasons.
researchers in the UK
are looking for funding to conduct a trial comparing adherence rates and
outcomes between people starting ART with Atripla
and those starting on the component drugs tenofovir, emtricitabine and
argue that comparing people starting on the two different formulations doesn’t
account for the fact that switching in itself may exact some penalty, and
instead suggest a trial design in which 50% of participants are randomised to
switch away from their existing Atripla
to the component drugs.
level of generic switching is to substitute one drug for another that is
closely equivalent: an example from outside the HIV field would be the
cholesterol-lowering statins, where one of the most powerful, rosuvastatin, is
still on patent as Crestor but the others are all available as
generics. Inside HIV, one example would be switching branded emtricitabine, as Emtriva or in Truvada, Atripla or Eviplera, for generic lamivudine. These
drugs are thought to be closely similar in efficacy.
identical, though. One recent study from France9 compared people on
regimens including tenofovir/emtricitabine with ones taking
tenofovir/lamivudine. It found that although the two drugs were comparably
effective, if lamivudine-containing regimens stopped working, people’s HIV was
more likely to develop drug resistance than if emtricitabine-based regimens
failed, even though resistance to these two drugs is conveyed by the same
mutation in HIV.
controversial would be a switch already done in some areas for reasons of cost:
using abacavir instead of tenofovir in people’s first regimen. We have
previously covered the decision in London (see HTU 205 and 212) to offer patients abacavir as first preference; as yet we
don’t have the results from audits to know whether there has been any change in
the efficacy, tolerability or adherence to first-line regimens as a result.
There is still argument as to whether abacavir is less efficacious in people
with high viral loads, or associated with more heart attacks.
Actually switching people to generic abacavir once it became available, says
Brian Gazzard, “would need to be re-discussed in some detail”; he isn’t sure
how acceptable it would be.
there’s the option of switching from a once-daily regimen to a twice-daily one.
Here the data are clear: taking pills twice a day is associated with
significantly poorer adherence. In the study quoted above,10
adherence was 3% higher in people on once-a-day compared to twice-a-day
regimens, 4% higher if they were new to ART and 7% higher if they had already
experienced treatment failure on one regimen with a detectable viral load. In
terms of clinical efficacy, there was no difference, but it’s clear a lot of
people wouldn’t like it.